scholarly journals Nicotine oxidation by genetic variants of CYP 2B6 and in human brain microsomes

2019 ◽  
Vol 7 (2) ◽  
pp. e00468 ◽  
Author(s):  
Adam Joseph Bloom ◽  
Pan‐Fen Wang ◽  
Evan D. Kharasch
Keyword(s):  
Human Brain ◽  
Genetic Variants ◽  
Brain Microsomes

Principles of evolutionary theory, evolutionary psychopathology, and genetics

2015 ◽  
pp. 3-40
Author(s):  
Martin Brüne
Keyword(s):  
Sexual Selection ◽  
Human Brain ◽  
Psychosomatic Medicine ◽  
Genetic Variants ◽  
Driving Force ◽  
Human Cognition ◽  
Protective Effects ◽  
Changing Environments ◽  
Genes And Environment ◽  
Natural And Sexual Selection

Darwin’s work on evolution by natural and sexual selection is the central scientific framework in biology that explains how life developed through adaptation to changing environments. Evolution has been the driving force that has shaped the human brain and mind in the same way as it has formed somatic traits. Many adaptations pertaining to human cognition, emotions, and behaviour emerged in ancestral environments of evolutionary adaptedness, from which modern living conditions deviate in one way or another. Such ‘mismatches’ of evolved traits and current environments may cause vulnerability to dysfunctional operation of cognitive, emotional, and behavioural traits. Genes and environment interact in manifold ways, yet genetic plasticity may not only convey vulnerability to dysfunction. Instead, the very same genetic variants that may lead to dysfunction when associated with environmental adversity exert protective effects against dysfunction when environments are more favourable. These insights have yet to be acknowledged by psychiatry and psychosomatic medicine.

scholarly journals Characterizing the Causal Pathway for Genetic Variants Associated with Neurological Phenotypes Using Human Brain-Derived Proteome Data

2020 ◽  
Vol 106 (6) ◽  
pp. 885-892 ◽  
Author(s):  
Nelson K. Kibinge ◽  
Caroline L. Relton ◽  
Tom R. Gaunt ◽  
Tom G. Richardson
Keyword(s):  
Human Brain ◽  
Genetic Variants ◽  
Causal Pathway

Genetic Variants and Multiple Sclerosis Risk Gene SLC9A9 Expression in Distinct Human Brain Regions

2016 ◽  
Vol 54 (9) ◽  
pp. 6820-6826 ◽  
Author(s):  
Guiyou Liu ◽  
Fang Zhang ◽  
Yang Hu ◽  
Yongshuai Jiang ◽  
Zhongying Gong ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Human Brain ◽  
Genetic Variants ◽  
Brain Regions ◽  
Risk Gene ◽  
Multiple Sclerosis Risk

scholarly journals Characterization of a phenobarbital-inducible cytochrome P-450, NADPH-cytochrome P-450 reductase and reconstituted cytochrome P-450 mono-oxygenase system from rat brain. Evidence for constitutive presence in rat and human brain

1992 ◽  
Vol 288 (2) ◽  
pp. 483-488 ◽  
Author(s):  
H K Anandatheerthavarada ◽  
M R Boyd ◽  
V Ravindranath
Keyword(s):  
Human Brain ◽  
Rat Brain ◽  
Rat Liver ◽  
Specific Content ◽  
Nadph Cytochrome ◽  
Apparent Homogeneity ◽  
Brain Microsomes ◽  
Molecular Masses ◽  
Reconstituted System ◽  
Cytochrome P 450

Cytochrome P-450 was purified to apparent homogeneity from the brain microsomes of phenobarbital-treated rats. The specific content of the purified P-450 was 12.7 nmol/mg of protein. NADPH-cytochrome P-450 reductase (reductase) was also purified to apparent homogeneity from brain microsomes. The specific content was 34.7 mumol of cytochrome c reduced/min per mg of protein. The reduced carbon monoxide spectrum of purified P-450 exhibited a peak at 450 nm. Both the P-450 and the reductase moved as single bands on SDS/PAGE. The molecular masses of the purified P-450 and the reductase were determined to be 53.3 and 72.0 kDa respectively. The purified brain P-450 cross-reacted with antibodies to rat liver P-450IIB1/IIB2 when examined by Western immunoblotting, but no immunological similarity was observed with rat liver P-450IA1/IA2 or P-450IIE1. Purified rat brain reductase cross-reacted with antibodies to rat liver reductase. Further, immunoblot experiments with untreated rat and human brain microsomes using antisera to the purified rat brain P-450 and reductase indicated that these forms of P-450 and NADPH-cytochrome P-450 reductase exist constitutively in rat and human brain. Purified rat brain P-450 was reconstituted with purified NADPH-cytochrome P-450 reductase, deoxycholate and dilauroyl glyceryl 3-phosphocholine. NADPH-dependent N-demethylation of aminopyrine and morphine was observed in the reconstituted system. The catalytic-centre activities were 80.25 and 38.2 nmol of formaldehyde formed/min per nmol of P-450 respectively. The reconstituted system had a comparatively lower catalytic-centre activity for 7-ethoxycoumarin O-de-ethylase (10.5 nmol of product formed/min per nmol of P-450).

scholarly journals Genetic control of age-related gene expression and complex traits in the human brain

2017 ◽  
Author(s):  
Trevor Martin ◽  
Hunter B. Fraser
Keyword(s):  
Gene Expression ◽  
Human Brain ◽  
Neurodegenerative Diseases ◽  
Genetic Variants ◽  
Complex Traits ◽  
Molecular Mechanisms ◽  
Neurological Diseases ◽  
Expression Patterns ◽  
Related Gene ◽  
Age Related

AbstractAge is the primary risk factor for many of the most common human diseases—particularly neurodegenerative diseases—yet we currently have a very limited understanding of how each individual’s genome affects the aging process. Here we introduce a method to map genetic variants associated with age-related gene expression patterns, which we call temporal expression quantitative trait loci (teQTL). We found that these loci are markedly enriched in the human brain and are associated with neurodegenerative diseases such as Alzheimer’s disease and Creutzfeldt-Jakob disease. Examining potential molecular mechanisms, we found that age-related changes in DNA methylation can explain some cis-acting teQTLs, and that trans-acting teQTLs can be mediated by microRNAs. Our results suggest that genetic variants modifying age-related patterns of gene expression, acting through both cis- and trans-acting molecular mechanisms, could play a role in the pathogenesis of diverse neurological diseases.

scholarly journals Common variants contribute to intrinsic human brain functional networks

2020 ◽  
Author(s):  
Bingxin Zhao ◽  
Tengfei Li ◽  
Stephen M. Smith ◽  
Di Xiong ◽  
Xifeng Wang ◽  
...  
Keyword(s):  
Human Brain ◽  
Genetic Variants ◽  
Brain Function ◽  
Brain Activity ◽  
Well Being ◽  
Central Executive ◽  
Common Variants ◽  
Default Mode ◽  
Common Genetic Variants ◽  
Intrinsic Brain Activity

AbstractThe human brain remains active in the absence of explicit tasks and forms networks of correlated activity. Resting-state functional magnetic resonance imaging (rsfMRI) measures brain activity at rest, which has been linked with both cognitive and clinical outcomes. The genetic variants influencing human brain function are largely unknown. Here we utilized rsfMRI from 44,190 individuals of multiple ancestries (37,339 in the UK Biobank) to discover and validate the common genetic variants influencing intrinsic brain activity. We identified hundreds of novel genetic loci associated with intrinsic functional signatures (P < 2.8 × 10−11), including associations to the central executive, default mode, and salience networks involved in the triple network model of psychopathology. A number of intrinsic brain activity associated loci colocalized with brain disorder GWAS (e.g., Alzheimer’s disease, Parkinson’s disease, schizophrenia) and cognition, such as 19q13.32, 17q21.31, and 2p16.1. Particularly, we detected a colocalization between one (rs429358) of the two variants in the APOE ε4 locus and function of the default mode, central executive, attention, and visual networks. Genetic correlation analysis demonstrated shared genetic influences between brain function and brain structure in the same regions. We also detected significant genetic correlations with 26 other complex traits, such as ADHD, major depressive disorder, schizophrenia, intelligence, education, sleep, subjective well-being, and neuroticism. Common variants associated with intrinsic brain activity were enriched within regulatory element in brain tissues.

The CHRM3 gene is implicated in abnormal thalamo-orbital frontal cortex functional connectivity in first-episode treatment-naive patients with schizophrenia

2016 ◽  
Vol 46 (7) ◽  
pp. 1523-1534 ◽  
Author(s):  
Q. Wang ◽  
W. Cheng ◽  
M. Li ◽  
H. Ren ◽  
X. Hu ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Human Brain ◽  
Frontal Cortex ◽  
Genetic Variants ◽  
First Episode ◽  
Genome Wide Association Studies ◽  
Orbital Frontal Cortex ◽  
Orbital Cortex ◽  
Treatment Naïve ◽  
Left Thalamus

BackgroundThe genetic influences in human brain structure and function and impaired functional connectivities are the hallmarks of the schizophrenic brain. To explore how common genetic variants affect the connectivities in schizophrenia, we applied genome-wide association studies assaying the abnormal neural connectivities in schizophrenia as quantitative traits.MethodWe recruited 161 first-onset and treatment-naive patients with schizophrenia and 150 healthy controls. All the participants underwent scanning with a 3 T-magnetic resonance imaging scanner to acquire structural and functional imaging data and genotyping using the HumanOmniZhongHua-8 BeadChip. The brain-wide association study approach was employed to account for the inherent modular nature of brain connectivities.ResultsWe found differences in four abnormal functional connectivities [left rectus to left thalamus (REC.L–THA.L), left rectus to right thalamus (REC.L–THA.R), left superior orbital cortex to left thalamus (ORBsup.L–THA.L) and left superior orbital cortex to right thalamus (ORBsup.L–THA.R)] between the two groups. Univariate single nucleotide polymorphism (SNP)-based association revealed that the SNP rs6800381, located nearest to the CHRM3 (cholinergic receptor, muscarinic 3) gene, reached genomic significance (p = 1.768 × 10−8) using REC.L–THA.R as the phenotype. Multivariate gene-based association revealed that the FAM12A (family with sequence similarity 12, member A) gene nearly reached genomic significance (nominal p = 2.22 × 10–6, corrected p = 0.05).ConclusionsOverall, we identified the first evidence that the CHRM3 gene plays a role in abnormal thalamo-orbital frontal cortex functional connectivity in first-episode treatment-naive patients with schizophrenia. Identification of these genetic variants using neuroimaging genetics provides insights into the causes of variability in human brain development, and may help us determine the mechanisms of dysfunction in schizophrenia.

Flavin-containing monooxygenase mediated metabolism of psychoactive drugs by human brain microsomes

1995 ◽  
Vol 672 (1-2) ◽  
pp. 276-280 ◽  
Author(s):  
Shubhada Bhamre ◽  
Shripad V. Bhagwat ◽  
Susarla K. Shankar ◽  
Michael R. Boyd ◽  
Vijayalakshmi Ravindranath
Keyword(s):  
Human Brain ◽  
Psychoactive Drugs ◽  
Brain Microsomes

scholarly journals Common genetic variants and gene expression associated with white matter microstructure in the human brain

NeuroImage ◽  
2014 ◽  
Vol 97 ◽  
pp. 252-261 ◽  
Author(s):  
Emma Sprooten ◽  
Emma E. Knowles ◽  
D. Reese McKay ◽  
Harald H. Göring ◽  
Joanne E. Curran ◽  
...  
Keyword(s):  
Gene Expression ◽  
White Matter ◽  
Human Brain ◽  
Genetic Variants ◽  
White Matter Microstructure ◽  
Common Genetic Variants
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